Abstract：
:S-Adenosylhomocysteine (AdoHcy), formed after the donation of the methyl group of S-adenosylmethionine to a methyl acceptor, is hydrolyzed to adenosine and homocysteine by AdoHcy hydrolase physiologically. The administration of the inhibitors of AdoHcy hydrolase to cells or animals normally results in an accumulation of cellular AdoHcy higher than those found in controls, which is often accompanied by a simultaneous rise in S-adenosylmethionine because of the feedback inhibition by AdoHcy on most methylation reactions. AdoHcy hydrolase has become a tantalizing pharmacological target for inhibition since its blockade can affect cellular methylation of phospholipids, proteins, small molecules, DNA, and RNA. Indeed, all of these different methylation reactions have been found to be inhibitable by the nucleoside inhibitors/substrates of AdoHcy hydrolase. Among the interesting effects are the activation of genes, induction of cellular differentiation, increased expression of transcription factors, and sometimes the repression of genes. Furthermore, some of the nucleosides show remarkable antiviral activities in vitro and in vivo. However, the mode of action of the inhibitors appears complex. Although the inhibition of methylation might account for some of the biological effects, the ability of some of the nucleoside inhibitors to undergo metabolic phosphorylation to nucleotides may account for part of their biological activities. The defining mode of action responsible for their biological effects still awaits biochemical elaboration, especially regarding their antiviral effects, induction of genes, or cellular differentiation.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Chiang PKdoi
10.1016/s0163-7258(97)00089-2subject
Has Abstractpub_date
1998-02-01 00:00:00pages
115-34issue
2eissn
0163-7258issn
1879-016Xpii
S0163-7258(97)00089-2journal_volume
77pub_type
杂志文章,评审abstract：:Progranulin (PGRN) is abundantly expressed in epithelial cells, immune cells, neurons, and chondrocytes, and reportedly contributes to tumorigenesis. PGRN is a crucial mediator of wound healing and tissue repair. PGRN also functions as a neurotrophic factor and mutations in the PGRN gene resulting in partial loss of t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.10.003
更新日期：2012-01-01 00:00:00
abstract：:The use of Translocator Protein 18 kDa (TSPO) as a clinical neuroimaging biomarker of brain injury and neuroinflammation has increased exponentially in the last decade. There has been a furious pace in the development of new radiotracers for TSPO positron emission tomography (PET) imaging and its use has now been exte...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.09.003
更新日期：2019-02-01 00:00:00
abstract：:This review provides biochemical, analytical, and biological background information relating to beta-N-acetylhexosaminidase (HexNAc'ase; EC 3.2.1.52) as an emerging target for the design of low-molecular-weight antifungals. The article includes the following: (1) a biochemical description of HexNAc'ase (reaction catal...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00110-1
更新日期：1997-10-01 00:00:00
abstract：:Methamphetamine (METH) abuse is a major public health issue around the world, yet there are currently no effective pharmacotherapies for the treatment of METH addiction. METH is a potent psychostimulant that increases extracellular dopamine levels by targeting the dopamine transporter (DAT) and alters neuronal activit...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.01.009
更新日期：2018-06-01 00:00:00
abstract：:The tropomyosin receptor kinase (TRK) family includes TRKA, TRKB, and TRKC proteins, which are encoded by NTRK1, NTRK2 and NTRK3 genes, respectively. Binding of neurotrophins to TRK proteins induces receptor dimerization, phosphorylation, and activation of the downstream signaling cascades via PI3K, RAS/MAPK/ERK, and ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.02.006
更新日期：2017-05-01 00:00:00
abstract：:During the past decade, it has become evident that dopamine plays an important role in the regulation of renal function and blood pressure. Dopamine exerts its actions via a class of cell-surface receptors coupled to G-proteins that belong to the rhodopsin family. Dopamine receptors have been classified into two famil...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00027-8
更新日期：1998-11-01 00:00:00
abstract：:The endothelins and sarafotoxins are two structurally related families of potent vasoactive peptides. Although the physiological functions of these peptides are not entirely clear, the endothelins are probably involved in pathophysiological conditions such as hypertension and heart failure. This review summarizes the ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90030-4
更新日期：1992-01-01 00:00:00
abstract：:As the first-line antimalarial drugs, artemisinins gained wide acceptance after the emergence of resistance to chloroquine in the 1950s. Artemisinin-based drugs have saved lives, especially in developing countries. The discovery of artemisinin was unique, timely, and fascinating, and the benefits of artemisinin were w...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107658
更新日期：2020-12-01 00:00:00
abstract：:Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) was initially identified as the major receptor for oxidized LDL (OxLDL) in endothelial cells. Its inducible expression in macrophages and smooth muscle cell was also observed. LOX-1 is a Type II membrane protein with a typical C-type lectin structur...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00236-x
更新日期：2002-07-01 00:00:00
abstract：:The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been admin...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.11.010
更新日期：2019-05-01 00:00:00
abstract：:Artemisinins are a unique class of antimalarial drugs with significant potential for drug repurposing for a wide range of diseases including cancer. Cancer is a leading cause of death globally and the majority of cancer related deaths occur in Low and Middle Income Countries (LMICs) where conventional treatment option...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107706
更新日期：2020-12-01 00:00:00
abstract：:In the search for new approaches to cancer therapy, the first alkyllysophospholipid (ALP) analogs were designed and studied about two decades ago, either as potential immunomodulators or as antimetabolites of phospholipid metabolism. In the meantime, it has been demonstrated that they really act in this way. However, ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)00001-w
更新日期：1995-04-01 00:00:00
abstract：:The understanding of renal fibrosis in chronic kidney disease (CKD) remains as a challenge. More than 10% of the population of developed countries suffer from CKD. Proliferation and activation of myofibroblasts and accumulation of extracellular matrix proteins are the main features of kidney fibrosis, a process in whi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.10.003
更新日期：2015-12-01 00:00:00
abstract：:Multiple sclerosis (MS) is the commonest cause of progressive neurological disability amongst young, Caucasian adults. MS is considered to be an auto-immune disease that results from an attack against myelin, the layer which surrounds axons. The pathophysiology of MS is complex, with both demyelination and axonal dege...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.01.006
更新日期：2010-04-01 00:00:00
abstract：:Sonodynamic therapy (SDT), which involves a combination of low-intensity ultrasound and chemotherapeutic agents called sonosensitizers, has been developed for its promising, distinct advantages, such as its noninvasive nature relative to traditional surgery and radiotherapy, greater accessibility to treat deeply locat...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.12.004
更新日期：2016-06-01 00:00:00
abstract：:Initially regarded as "epigenetic modifiers" acting predominantly through chromatin remodeling via histone acetylation, HDACIs, alternatively referred to as lysine deacetylase or simply deacetylase inhibitors, have since been recognized to exert multiple cytotoxic actions in cancer cells, often through acetylation of ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.04.004
更新日期：2014-09-01 00:00:00
abstract：:The vascular endothelium not only is a single monolayer of cells between the vessel lumen and the intimal wall, but also plays an important role by controlling vascular function and structure mainly via the production of nitric oxide (NO). The so called "cardiovascular risk factors" are associated with endothelial dys...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.06.003
更新日期：2014-12-01 00:00:00
abstract：:The past three decades have witnessed a welcome expansion of the therapeutic armamentarium for the management of pulmonary arterial hypertension (PAH). However, against this backdrop, there have been some notable disappointments in drug development. Here we use these as case studies to emphasize the importance of info...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.04.012
更新日期：2016-08-01 00:00:00
abstract：:Type I signal peptidases are essential membrane-bound serine proteases that function to cleave the amino-terminal signal peptide extension from proteins that are translocated across biological membranes. The bacterial signal peptidases are unique serine proteases that utilize a Ser/Lys catalytic dyad mechanism in plac...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章
doi：10.1016/s0163-7258(00)00064-4
更新日期：2000-07-01 00:00:00
abstract：:Elevated low density lipoprotein cholesterol (LDL-C) levels have been associated with an increased risk for cardiovascular disease (CVD). Despite a 25-30% reduction in CVD risk with LDL-C reducing strategies, there is still a significant residual risk. Moreover, achieving target LDL-C values in individuals at high CVD...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.03.005
更新日期：2012-07-01 00:00:00
abstract：:Portal hypertension (PHT) is a common clinical syndrome associated with chronic liver diseases; it is characterized by a pathological increase in portal pressure. Pharmacotherapy for PHT is aimed at reducing both intrahepatic vascular tone and elevated splanchnic blood flow. Due to the altered hemodynamic profile in P...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(01)00128-0
更新日期：2001-03-01 00:00:00
abstract：:Chitinase 3-like 1 (CHI3L1) is a secreted glycoprotein that mediates inflammation, macrophage polarization, apoptosis, and carcinogenesis. The expression of CHI3L1 is strongly increased by various inflammatory and immunological conditions, including rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, and se...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2019.107394
更新日期：2019-11-01 00:00:00
abstract：:The leukotrienes are synthesized from essential fatty acids via a 5-lipoxygenase enzyme. Most is known about the four-series leukotrienes derived from arachidonic acid. Leukotriene B4 is a potent chemotactic agent for leukocytes and it induces neutrophil-dependent increased microvascular permeability. Leukotrienes C4,...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90035-z
更新日期：1990-01-01 00:00:00
abstract：:It is surprising that only relatively recently has attention been directed to the characterization of the properties of acid ribonucleases (RNases), leading to some understanding of their biochemistry and their functional roles. The present review summarizes current progress in this field under the following general t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00035-7
更新日期：1999-02-01 00:00:00
abstract：:G protein-gated inwardly rectifying potassium channels (Kir3/GirK) are important for maintaining resting membrane potential, cell excitability and inhibitory neurotransmission. Coupled to numerous G protein-coupled receptors (GPCRs), they mediate the effects of many neurotransmitters, neuromodulators and hormones cont...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2021.107808
更新日期：2021-01-18 00:00:00
abstract：:Nucleoside monophosphate kinases catalyze the reversible phosphotransferase reaction between nucleoside triphosphates and monophosphates, i.e., monophosphates are converted to their corresponding diphosphate form. These enzymes play an important role in the synthesis of nucleotides that are required for a variety of c...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(00)00048-6
更新日期：2000-08-01 00:00:00
abstract：:Evidence has accumulated indicating that the interaction between NO and the autonomic nervous system plays an important role in cardiovascular regulation, not only in experimental animals, but also in humans. NO interacts with the autonomic nervous system both at the central level and peripherally. In this review, we ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.11.009
更新日期：2005-05-01 00:00:00
abstract：:Current treatment of human immunodeficiency virus-1 (HIV-1) infection is effective, although it does not permanently suppress viral replication in all patients. Viral persistence, drug toxicity, and antiretroviral resistance are challenging barriers to successful treatment of HIV-1 infection. It has become increasingl...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.06.007
更新日期：2011-12-01 00:00:00
abstract：:Drug candidate and toxicity screening processes currently rely on results from early-stage in vitro cell-based assays expected to faithfully represent essential aspects of in vivo pharmacology and toxicology. Several in vitro designs are optimized for high throughput to benefit screening efficiencies, allowing the ent...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.01.001
更新日期：2012-04-01 00:00:00
abstract：:Functional polymorphisms that alter gene expression and mRNA processing appear to play a critical role in shaping human phenotypic variability. Intensive studies on polymorphisms affecting drug response have revealed multiple modes of altered gene function, frequently involving cis-acting regulatory sequence variants....
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.11.001
更新日期：2005-04-01 00:00:00
